Long-Term Effect of Post-traumatic Stress in Adolescence on Dendrite Development and H3K9me2/BDNF Expression in Male Rat Hippocampus and Prefrontal Cortex

Abstract

Exposure to a harsh environment in early life increases in the risk of post-traumatic stress disorder (PTSD) of an individual. Brain derived neurotrophic factor (BDNF) plays an important role in neurodevelopment in developmental stages. Both chronic and traumatic stresses induce a decrease in the level of BDNF and reduce neural plasticity, which is linked to the pathogenesis of PTSD. Also, studies have shown that stress alters the epigenetic marker H3K9me2, which can bind to the promoter region of the Bdnf gene and reduce BDNF protein level. However, the long-term effects of traumatic stress during adolescence on H3K9me2, BDNF expression and dendrite development are not well-known. The present study established a model of PTSD in adolescent rats using an inescapable foot shock (IFS) procedure. Anxiety-like behaviors, social interaction behavior and memory function were assessed by the open field test, elevated plus maze test, three-chamber sociability test and Morris water maze test. In addition, neuronal development and H3K9me2/BDNF expression in hippocampus (HIP) and prefrontal cortex (PFC) were evaluated by Golgi staining, western blotting, qRT-PCR analysis and CHIP-qPCR analysis. Additionally, the Unc0642, a small molecule inhibitor of histone methyltransferase (EHMT2) was used for intervention. The results showed that the IFS procedure induced the PTSD-like behaviors in rats, resulted in fewer dendrite branches and shorter dendrite length in CA1 of HIP and PFC, increased H3K9me2 level and decreased BDNF expression in HIP and PFC. Also, although all the changes can persist to adulthood, Unc0642 administration relieved most of alterations. Our study suggests that traumatic stress in adolescence leads to immediate and long-term mental disorders, neuronal morphological changes, lower BDNF level and increased H3K9me2 level in the HIP and PFC, indicating that H3K9me2/BDNF dysfunction plays a key role in pathogenesis of PTSD.

A novel arousal-based individual screening reveals susceptibility and resilience to PTSD-like phenotypes in mice

“…Moreover, the upregulation of BDNF in the HIP of susceptible mice is in line with previous studies showing an increased BDNF in the hippocampus of rodents exhibiting PTSD like phenotypes ( Sharma et al, 2020 ; Zhang et al, 2014 ). On the other hand, these results do not corroborate previous findings reporting a decreased BDNF mRNA/protein in mPFC and HIP of rodents tested in other preclinical models of PTSD ( Ni et al, 2020 ; Zhao et al, 2020 ). One possible explanation in this case is that this increased BDNF mRNA in the mPFC might represent a not sufficient compensatory mechanism aim at counteract a blunted cortical BDNF signaling, which has been linked to maladaptive fear memory responses/fear extinction deficits ( Kataoka et al, 2019 ).…”

Inhibiting Brd4 alleviated PTSD‐like behaviors and fear memory through regulating immediate early genes expression and neuroinflammation in rats

“…IFS could induce PTSD symptoms in rodents; the freezing behavior in the contextual and cue fear test was used to evaluate PTSD core symptoms (Bali & Jaggi, 2015). Consistent with previous findings, the rats in the IFS group displayed depression/anxiety‐like behaviors and deficit in spatial memory (Zhao et al., 2020), as well as freezing to conditioned context and auditory signals, indicating that the IFS was a valid procedure (Li et al., 2020; Wang et al., 2018). In fact, stressors such as restraint and single prolonged shock usually are used to develop PTSD animal models.…”

“…The procedure was modified to establish a PTSD model as described previously (Wang, Wang, et al., 2018; Zhao et al., 2020). All modeling was performed during a light cycle, by two experimenters blinded to the experimental group.…”

PRG-1 relieves pain and depressive-like behaviors in rats of bone cancer pain by regulation of dendritic spine in hippocampus

“…), the brains of rats were removed and immediately stained by Hito Golgi-Cox OptimStain TM Kit (Hito-biotec, USA) according to the manufacturer's protocol and then photographed under a light microscope. Spines were defined as dendritic protrusions and were manually counted along a selected dendritic segment using ImageJ 6.0 software (NIH, USA) [74,75]. In brain sections we focus our analyses on dendrites of three areas: (1) the middle molecular layer of dentate gyri (moDG) granule cells; (2) stratum radiatum (sr, apical dendrites) and (3) stratum oriens (so, basal dendrites) of pyramidal neurons of the CA1 region.…”